Table 1 ADMSCs effectively participate in liver regeneration in the treatment of various liver diseases

2 × 10⁶

Tail vein

N/A

Liver transplantation

Rat

Decrease the apoptosis of hepatocytes; decrease the levels of ALT, AST, and TBIL; maintain the tissue structure

Decrease the expression of IL-2 and IL-10

[90]

1 × 10⁵

Jugular vein

N/A

70% partial hepatectomy

Mice

Liver regeneration

Integration of ADMSCs into the liver

[86]

1-2 × 10⁶

Tail vein

Before ischemia

70% partial hepatectomy

Mice

Improve histopathological changes; decrease serum levels of hepatocyte markers

Enhance hepatocyte proliferation

[91]

4 × 10⁶

Liver lobe

N/A

Bulldog clamp for 90 min and clamp removal

Rats

Decrease necrotic areas and improve liver function

Suppress the proinflammatory cytokines IL-6, IL-21, and CD70; activate the NOTCH Pathway

[92]

2 × 10⁶

Portal vein

N/A

Repeated partial hepatectomy

Rats

Increase body weight ratio; improve liver function; improve PCNA-labeling index

Upregulate expression of HGF

[84]

1 × 10⁶/kg

Liver parenchyma

N/A

Partial hepatectomy

Pigs

Reduce pathological and ultrastructural changes and decrease the number of apoptosis-positive cells

Downregulate the expression of Fas, Fas ligand, caspase-3, caspase-8, and caspase-9; upregulate of the ratio of Bcl-2/Bax

[93]

Decrease the serum levels of ALT, AST, TBIL, and LDH

Upregulate the expression of SOD; suppress the expression of MPO and MDA; suppress autophagy

[94]

1.2 × 10⁶

Liver lobe

N/A

Occlude the vascular supply of the left lobe of the liver for 60 m followed by reperfusion for 72 h

Rats

Reduce plasma aminotransferases; promote liver regeneration

Suppress cellular activation; reduce proinflammatory cytokine release; alleviate oxidative stress; preserve hepatic microcirculation; decrease apoptosis

[95]

2 × 10⁶

Intravenous

Overexpression of MiR-27b

PH

Rats

Enhance liver regeneration and preserve hepatic function

Downregulate the expression of inflammatory cytokines; upregulate the expression of HGF, HO-1, and mitochondrial biogenesis in a PGC-1α-dependent manner

[85]

1–2 × 10⁶

Tail vein

Before CCl₄

CCl₄

Mice

Decrease levels of ALT and serum IL-6; increase the expression of regeneration markers and PCNA; improve histopathology; improve survival rate

Inhibit inflammation and liver necrosis

[97]

4 × 107 cells/kg

Spleen

Spheroid

CCl₄

Mice

Increase liver regeneration

Inhibit hepatocyte necrosis

[98]

1 × 10⁶

Liver lobe

RSF

CCl₄

Mice

Increase the survival rate of ALF animals

Upregulate angiogenesis and hepatogenic differentiation

[99]

1.0 × 10⁶

Intravenously

N/A

Con A

Mice

Increase the survival rate of ConA-induced fulminant hepatitis mice; decrease liver enzyme levels; improve histopathological changes

Suppress inflammatory cytokines

[100]

1 × 10⁵

Tail vein

N/A

Con A

Mice

Liver histology showed an almost normal appearance, with no necrosis

Repress inflammatory cell accumulation

[101]

1.0 × 10⁶

Tail vein

N/A

Con A

Mice

Decrease liver enzyme levels; improve histopathological changes

Decrease inflammation related to IL-6, IL-10, IFN-γ, and TNF-α

[102]

2 × 10⁶

Tail vein

LPA and/or S1P

Gal/LPS

Mice

Enhance survival rate of Gal/LPS-induced ALF mice; ameliorate histological damage;

Reduce oxidative stress, inflammation and lipid metabolism dysfunction

[103]

2 × 10⁶

Tail vein

ZD

Gal/LPS

Mice

Improve liver function of ALF model; exert no adverse effects on healthy animals

Activation of the PKC/Raf-1/MAPK/NF-κB pathway; upregulate microRNA-210

[104]

1.0 × 10⁶

Tail vein

N/A

CCl₄

Mice

Reduce serum levels of glutamic pyruvate transaminase and TBIL; reduce hepatocyte vacuolar degeneration; decrease serum transaminase levels; inhibit liver fibrogenesis

Increase MMP-3 and MMP-9 levels

[105]

1.0 × 10⁶

Liver lobe

N/A

Thioacetamide

Rats

Eliminate liver fibrosis

Hepatic differentiation; reduce inflammation and inhibit HSC activation

[106]

5 × 10⁶

Portal vein

N/A

CCl₄

Rats

Reduce the fibrotic area; reduce the expression of collagen I and a-SMA in the liver; reduce hydroxyproline level in the live; reduce collagen III and hyaluronic acid levels; inhibit liver fibrogenesis

Inhibit the proliferation and activation of HSCs; enhance HSC apoptosis; increase HGF level; decrease levels of NGF and TGF-b1

[107]

3 × 10⁵/kg and 6.6 × 10⁵/kg

Hepatic artery

N/A

Cirrhosis

Patients

Improve liver function

Increase serum HGF and IL-6 concentrations

[108]

5 × 10⁶

Caudal vein

Splenectomy

CCl₄

Rats

Improve liver function; reduce levels of α-SMA and TGF-β; suppress liver fibrosis

Upregulate the levels of stromal cell-derived factor 1 and HGF; enhance the migration of ADMSCs into injured sites; promotes HSC apoptosis

[109]

1.5 × 10⁶

Intrahepatic

Serum from acute CCl4 injury rat

CCl₄

Rats

Improve liver functions; reduce liver fibrosis

Increase the homing of ADMSCs

[110]

1.5 × 10⁶

Tail vein

Overexpression of FGF21

Thioacetamide

Mice

Decrease serum hyaluronic acid; reduce serum ALT, AST, and hyaluronic acid levels; reduce expression of fibrosis-related factors such as α-SMA, collagen and TIMP-1;

Inhibition of p-JNK, NF-κB, and p-Smad2/3 signaling and secretion of LA and LTF

[111]

1 × 10⁵

Tail vein

Overexpression of MiR-122

CCl₄

Mice

Decrease serum levels of ALT, AST, and liver hydroxyproline content; reduce mature Col1A1 protein level

Suppress the proliferation of and collagen maturation in HSCs; decrease the expression levels of TGF-β1 and α-SMA in the liver

[112]